Gas chromatography (hereafter, “GC”) is a widely used method for the analysis of chemical compounds. It is used in a large number of applications, including but not limited to forensics, exhaust gas monitoring, environmental analysis, and industrial process monitoring.
In GC, a sample of analyte vapor (hereafter, “analyte”) is introduced, typically with a carrier gas, into a small capillary or column. The interior diameter of the column is coated with a thin film, known as a “stationary phase.” The various components of the analyte have different affinities for the stationary phase and the carrier gas. As a result of the flow of carrier gas through the column, the components of the analyte move through the column at different average rates and (ideally) separate from one another. As they exit the column, the separated components of the analyte can be detected with a number of different detectors, such as a flame ionization detector and/or a mass spectrometer. Because the analyte is exposed to a column containing a single stationary phase, this type of GC is often referred to as one-dimensional GC (hereafter, “1D GC”).
When an analyte contains a number of compounds that have similar affinity to a stationary phase, separation of those compounds using 1D GC may be difficult or impossible. To address this issue, two dimensional (2D) GC, or GC×GC systems have been developed. In general, 2D GC systems include two chromatography columns that are coupled in series. The interior diameter of each column is coated with a different stationary phase. In this way, compounds having similar affinity (e.g., boiling point and/or polarity) for the stationary phase of the first column may be separated due to their differing affinity (orthogonality) for the stationary phase of the second column. As a result, compounds that would normally co-elute in a 1D GC system can be separated using 2D GC.
Although 2D GC can enable the separation of a wide variety of compounds, it is possible that bands of analyte compounds separated in the first column may co-elute with bands of analyte compounds separated in the second column. As a result, errors may be introduced into the analysis of the sample. To address this issue, devices for trapping and accumulating analyte from the first column of the 2D GC while conducting analysis in the second column of the 2D GC have been proposed. In particular, devices known as thermal modulators have been placed between the first column and the second column.
A basic diagram outlining the construction of a 2D GC incorporating a thermal modulator is shown in FIG. 1. As shown, 2D GC 100 includes first column 110 including a first stationary phase, and second column 130 including a second stationary phase. First column 110 and second column 130 are coupled in series by thermal modulator 120. Carrier gas and analyte are injected into first column 110, and separated components of the analyte exit second column 130. Upon exiting second column 130, the separated compounds enter the inlet of a detector 140.
Thermal modulator 120 includes a short segment of capillary, hereafter referred to as a “modulator column.” The modulator column is rapidly cooled so as to trap the analyte leaving first column 110 within the modulator column. For example, the modulator column may be cooled to −40° C. for 1-10 seconds to accumulate (trap) analyte peaks from the first column. The modulator column may then be rapidly heated to a high temperature (e.g., 100-300° C.) to vaporize the trapped analyte and release it to second column 130. By repeatedly cycling (i.e., thermally modulating) the modulator column from between a low temperature and a high temperature, “pulses” of analyte from first column 110 are eluted into second column 130. Because only a single section of the modulator column is modulated, modulator 120 is referred to herein as a “single stage thermal modulator.”
Put in other terms, thermal modulator 120 acts as an alternating trap and injector. That is, thermal modulator 120 continually traps, focuses, and re-injects analyte at a user defined time constant throughout the analysis of a sample, as described below. Because thermal modulator 120 focuses the analyte peaks in a modulator column, a 2D GC system can exhibit improved signal to noise relative to 1D GC system. As a result, 2D GC instruments often can detect smaller quantities of components within an analyte than 1D GC instruments, in addition to providing the separation benefits noted above.
To illustrate the performance of 2D GC, relative to 1D GC, reference is made to FIGS. 2A and 2B, which plot the results of an analysis of the same sample by 1D GC (FIG. 2A) and 2D GC (FIG. 2B). As shown, significantly more peaks can be identified using 2D GC (FIG. 2B) than 1D GC (FIG. 2A).
In order to achieve desirably narrow second dimension peak widths, many commercial 2D GC instruments employ a cryogenic cooling system. In such systems, cold focusing in the modulator is achieved by rapidly cooling and warming the modulator column, as described above. Rapid cooling may be achieved, for example, by intermittently directing liquid nitrogen (LN2), a cooled gas, or liquid carbon dioxide onto the modulator column. In contrast, rapid heating may be accomplished with a hot gas (e.g. nitrogen) jet. Although cooling and heating a modulator column in this manner is effective, it requires the use of a large quantity of costly consumables. Moreover, it limits the use of many 2D GC systems to the laboratory. As such, many 2D GC systems cannot be employed as a portable instrument.
Investigation has been made into the development of a liquid cooled, single stage thermal modulator in which the modulator column is cooled by a cold “finger” and an immersion cooler. While this technique eliminates the use of cryogens, the size of the cold finger and immersion cooler still limit the portability of the instrument.
In addition to portability limitations, many 2D GC instruments utilize single stage modulators, such as described above. In these instruments, the minimum peak width that the single stage thermal modulator can transfer to the second column may be limited. To permit the delivery of even narrower (i.e., more focused) peaks to the second column, two stage thermal modulators have been proposed. Generally, a two stage thermal modulator operates by independently heating and cooling two sections (stages) of a single modulator column. This technique allows peaks from the first column to be focused more tightly in the second stage of the modulator column, prior to transfer to the second column of the 2D GC. As a result, two stage modulators can produce narrower and higher peaks, resulting in both improved separation and improved sensitivity, relative to 1D GC or 2D GC systems employing a single stage thermal modulator.
Like single stage modulators, investigation has been made into two stage thermal modulators that are liquid cooled. While such systems have shown some promise, their performance is limited due to the size of the cooling system and the presence of a chilled region or “spot” between the two stages of the modulator column. This cold spot can hinder or even inhibit transfer of analyte peaks from the first stage to the second stage of the modulator, and potentially to the second column of the instrument. Even if analyte passes through the modulator to the second column, the cold spot can distort peak shape, or give rise to other artifacts, such as memory and bleed.